Extracellular matrix adhesins of Treponema pallidum

描述(申请人提供)：由螺旋体引起的梅毒 梅毒螺旋体亚种。梅毒是一种慢性细菌感染 这仍然是一个全球公共卫生问题，估计有1200万人 发展中国家、东欧和南欧国家报告的新病例 美国。在缺乏适当的抗生素治疗的情况下，梅毒螺旋体 建立一种终生慢性感染，可能会进展到虚弱 在大约三分之一的感染者中有可能致命的第三种疾病 个人。除了疾病本身的严重性质外，一些 研究表明梅毒感染可能会增加感染的风险 人类免疫缺陷病毒的传播。第一步是建立一个 梅毒螺旋体感染是细菌附着和定植上皮 表面。因此，预防梅毒螺旋体感染的合理方法 是开发抑制细菌附着到宿主细胞的方法。 本提案中概述的研究重点是T。 梅毒粘附素参与宿主细胞附着，特别是那些 参与附着细胞外基质(ECM)的成分。这个 梅毒螺旋体的粘附素将通过各种实验方法进行鉴定 技术，包括亲和层析和表达文库筛选。 推测的粘附素将以重组形式表达，使用异源 表达系统。这些蛋白质随后将被研究其 通过确定它们与宿主细胞的结合潜能参与宿主细胞的附着 宿主细胞和ECM组件。确认的粘附素将进行测试以确定其 补充非粘附型梅毒螺旋体生物型赖特的能力， 以及梅毒螺旋体粘附素和细胞外基质成分的分子区域 负责附着的人将被确定。梅毒螺旋体粘附素将 还分析了它们在兔免疫中的免疫保护潜力 并挑战实验，特别是它们防止 梅毒螺旋体感染。本报告概述的研究的长期目标 建议鉴定梅毒螺旋体ECM-粘附素，这反过来将有助于 进一步了解梅毒螺旋体所涉及的分子 发病机制，并确定潜在的梅毒疫苗候选。

DESCRIPTION (Provided by the applicant): Syphilis, caused by the spirochete bacterium Treponema pallidum subsp. pallidum, is a chronic bacterial infection that remains a public health concern worldwide, with an estimated 12 million new cases reported in developing nations, Eastern Europe, and the Southern United States. In the absence of appropriate antibiotic treatment, T. pallidum establishes a lifelong chronic infection that may progress to the debilitating and potentially fatal tertiary disease in approximately one third of infected individuals. Apart from the serious nature of the disease itself, a number of studies suggest syphilis infections may increase the risk of acquisition and transmission of human immunodeficiency virus. The first step in establishing a T. pallidum infection is bacterial attachment and colonization of epithelial surfaces. Consequently, a logical approach for preventing T. pallidum infection is to develop methodologies for inhibiting bacterial attachment to host cells. The studies outlined in this proposal focus upon the identification of T. pallidum adhesins involved in host cell attachment, and specifically those involved in attaching to components of the extracellular matrix (ECM). The adhesins of T. pallidum will be identified using a variety of experimental techniques, including affinity chromatography and expression library screening. Putative adhesins will be expressed in a recombinant form using heterologous expression systems. These proteins will subsequently be investigated for their involvement in host cell attachment by determining their binding potential to host cells and ECM components. Confirmed adhesins will be tested for their ability to complement the non-adherent treponeme T. phagedenis biotype Reiter, and the molecular regions of the treponemal adhesins and ECM components responsible for attachment will be identified. The T. pallidum adhesins will also be analyzed for their immunoprotective potential in rabbit immunization and challenge experiments, and specifically for their ability to prevent treponemal infection. The long-term objective of the studies outlined in this proposal is to identify T. pallidum ECM-adhesins, which will in turn help to further our under-standing of the molecules involved in T. pallidum pathogenesis and identify potential syphilis vaccine candidates.